Silence Therapeutics' Zerlasiran: A Promising New Treatment for High Lp(a)

Silence Therapeutics, a global clinical stage biotechnology company, recently presented late-breaking Phase 2 data for its investigational drug zerlasiran at the 2024 American Heart Association (AHA) Annual Meeting. Zerlasiran, a short interfering RNA (siRNA) therapy, demonstrated significant reductions in lipoprotein(a) [Lp(a)] levels in patients with atherosclerotic cardiovascular disease (ASCVD) and high Lp(a) levels. These findings have the potential to transform the treatment landscape for patients with high Lp(a), a genetic risk factor for cardiovascular disease.

The ALPACAR-360 study, a multicenter, randomized, double-blind, placebo-controlled dose-finding Phase 2 trial, evaluated the efficacy and safety of zerlasiran in 178 patients with ASCVD and Lp(a) levels ≥125 nmol/L. Patients were randomly assigned to one of three active subcutaneous doses of zerlasiran (300 mg every 16 weeks, 300 mg every 24 weeks, or 450 mg every 24 weeks) or placebo. The primary endpoint was the time-averaged change in Lp(a) from baseline to 36 weeks.

The results of the study were encouraging, with all active doses of zerlasiran producing greater than 80% mean time-averaged placebo-adjusted reductions in Lp(a) concentrations over 36 weeks. Maximum Lp(a) reductions exceeded 90%, and the effects persisted for at least 60 weeks following the first dose. No safety concerns emerged with infrequent dosing. These findings suggest that zerlasiran has the potential to provide long-term reductions in Lp(a) with infrequent dosing, supporting its progression into Phase 3 trials.

The competitive profile of zerlasiran is further bolstered by its ability to provide long-term reductions in Lp(a) with infrequent dosing. This could make it an attractive option for patients and healthcare providers, potentially improving adherence and reducing healthcare costs. However, further analysis of the data, including safety and tolerability profiles, will help refine the optimal dose and dosing interval for Phase 3 trials.



In conclusion, Silence Therapeutics' Phase 2 results for zerlasiran demonstrate its potential as a promising new treatment for patients with high Lp(a). The drug's ability to effectively lower Lp(a) levels, along with its long-term durability and infrequent dosing, positions it favorably in the competitive landscape of cardiovascular disease treatments. As Silence Therapeutics progresses zerlasiran into Phase 3 trials, further research is needed to confirm these potential benefits and assess the economic impact on healthcare systems.